4-Methylmorpholine → HCID 10073837, compound

Participants

Reaction Steps

To a stirred solution of N1-[(2R,3S)-4-oxo-2-phenyl-2,3,4,5-tetrahydro-1,5-benzoxazepin-3-yl]-L-alaninamide (6g) (765 mg, 2.351 mmol) in dichloromethane (10 mL) was added 3,5-difluorophenylacetic acid (450 mg, 2.614 mmol), HOBt (441 mg, 3.265 mmol), NMM (330 mg, 3.267 mmol) and EDAC-HCl (626 mg, 3.265 mmol). The mixture was stirred at ambient temperature under nitrogen overnight. The solvent was evaporated and the residue partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The organic phase was separated and then washed in succession with 1N aqueous HCl and brine. The organic solution was dried, filtered and evaporated. The residue was purified by flash chromatography on silica gel eluting with 2:1 (v/v) ethyl acetate:hexanes to afford the title compound (968 mg, 86%) as a white solid. TLC Rf=0.30 (2:1 ethyl acetate:hexanes). 1H NMR (300 MHz, DMSO-d6) δ1.11 (d, 3H, J=7.0 Hz), 3.46 (q AB, 2H, J=14.4 Hz), 4.24 (m, 1H), 4.95 (m, 1H), 5.61 (d, 1H, J=6.6 Hz), 6.94 (m, 2H), 7.02-7.29 (m, 5H), 7.32-7.40, (m, 6H), 8.32 (m, 1H), 10.29 (br, 1H). MS APCI, m/z=480 (M+1). LC/MS: 2.31 min.

Provenance & Evidence